Magrolimab, Azacitidine, and Venetoclax for the Treatment of Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title: An Open-Label Phase IB/II Study of Magrolimab in Combination With Azacitidine and Venetoclax for the Treatment of Patients With Acute Myeloid Leukemia (AML)

Status Active, not recruiting

Clinical Trial Summary

This phase Ib/II trial studies the side effects and best dose of magrolimab and venetoclax when given together with azacitidine and to see how well they work in treating patients with acute myeloid leukemia. Magrolimab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving magrolimab, azacitidine, and venetoclax may help to control the disease.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the safety and maximum tolerable dose (MTD) of this combination in patients with acute myeloid leukemia (AML).

II. To determine the response rate (RR) including CR (complete remission) + CRi (complete remission with incomplete count recovery) within 3 months of treatment initiation of this combination in patients with AML.

SECONDARY OBJECTIVES:

I. To assess the CR + complete remission with partial hematological recovery (CRh) rate and morphologic leukemia free (MLF) rate within 3 months of treatment initiation of this combination in patients with AML.

II. To determine the duration of response (DOR), event-free survival (EFS), overall survival (OS), MRD status at response and best MRD response attained by flow-cytometry, 4- and 8-week mortality, and number of patients bridged to hematopoetic stem cell transplant (HSCT) and median duration to HSCT from the initiation of the combination.

III. To investigate correlations of response to this combination with a pre- therapy, on-therapy, and progression 81-gene panel of gene mutations in AML.

EXPLORATORY OBJECTIVES:

I. To investigate possible relationships between response and non-response to the combination with pretherapy, on-therapy, and progression gene expression signatures.

II. To investigate the characterization of genetic heterogeneity in tumor cell populations, by performing targeted single-cell sequencing on longitudinally collected AML tumor populations from patients using a novel microfluidic approach that barcodes amplified genomic deoxyribonucleic acid (DNA) from thousands of individual leukemia cells confined to droplets (single cell sequencing).

III. To identify individual cell populations (AML blasts, T-cells - both bulk and T-cell subsets and coreceptor/ligand expression, macrophages and their coreceptor/ligands) and how their signaling state in disease relates to clinical outcomes.

IV. To store and/or analyze surplus blood or tissue including bone marrow, if available, for potential future exploratory research into factors that may influence development of AML and/or response to the combination (where response is defined broadly to include efficacy, tolerability or safety).

OUTLINE: This is a phase Ib, dose-escalation study of venetoclax and magrolimab followed by a phase II study.

Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 30-60 minutes on days 1-7, venetoclax orally (PO) once daily (QD) on days 1-28 of cycle 1 (may be reduced to days 1-21 for subsequent cycles after principal investigator approval), and magrolimab IV over 2-3 hours on days 1, 4, 8, 11, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycle 2, and days 1 and 15 of cycle 3 and subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 100 days. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

• NCT number: NCT04435691
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 28, 2020
• Completion date: December 31, 2024